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Identification
HMDB Protein ID HMDBP00036
Secondary Accession Numbers
  • 5265
Name Histone acetyltransferase KAT5
Synonyms
  1. 60 kDa Tat-interactive protein
  2. HIV-1 Tat interactive protein
  3. Histone acetyltransferase HTATIP
  4. Lysine acetyltransferase 5
  5. Tip60
  6. cPLA(2)-interacting protein
Gene Name KAT5
Protein Type Enzyme
Biological Properties
General Function Involved in chromatin binding
Specific Function Catalytic subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Directly acetylates and activates ATM. In case of HIV-1 infection, interaction with the viral Tat protein leads to KAT5 polyubiquitination and targets it to degradation.
Pathways
  • HTLV-I infection
Reactions
Acetyl-CoA + [histone] → Coenzyme A + acetyl-[histone] details
GO Classification
Biological Process
histone acetylation
double-strand break repair
positive regulation of transcription, DNA-dependent
virus-host interaction
negative regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
transcription, DNA-dependent
androgen receptor signaling pathway
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
negative regulation of interleukin-2 production
regulation of growth
Cellular Component
nucleolus
perinuclear region of cytoplasm
transcription factor complex
Piccolo NuA4 histone acetyltransferase complex
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
organelle part
intracellular organelle part
chromosomal part
chromatin
Function
binding
catalytic activity
transferase activity
transferase activity, transferring acyl groups
transferase activity, transferring acyl groups other than amino-acyl groups
chromatin binding
Molecular Function
metal ion binding
transcription coactivator activity
androgen receptor binding
histone acetyltransferase activity
Process
cellular process
cellular component organization at cellular level
organelle organization
chromosome organization
chromatin organization
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
chromatin assembly or disassembly
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. nucleolus
  4. perinuclear region
Gene Properties
Chromosome Location 11
Locus 11q13
SNPs KAT5
Gene Sequence
>1542 bp
ATGGCGGAGGTGGGGGAGATAATCGAGGGCTGCCGCCTACCCGTGCTGCGGCGGAACCAG
GACAACGAAGATGAGTGGCCCCTGGCCGAGATCCTGAGCGTGAAGGACATCAGTGGCCGG
AAGCTTTTCTACGTCCATTACATTGACTTCAACAAACGTCTGGATGAATGGGTGACGCAT
GAGCGGCTGGACCTAAAGAAGATCCAGTTCCCCAAGAAAGAGGCCAAGACCCCCACTAAG
AACGGACTTCCTGGGTCCCGTCCTGGCTCTCCAGAGAGAGAGGTGCCGGCCTCGGCGCAG
GCCAGCGGGAAGACCTTGCCAATCCCGGTCCAGATCACACTCCGCTTCAACCTGCCCAAG
GAGCGGGAGGCCATTCCCGGTGGCGAGCCTGACCAGCCGCTCTCCTCCAGCTCCTGCCTG
CAGCCCAACCACCGCTCAACGAAACGGAAGGTGGAGGTGGTTTCACCAGCAACTCCAGTG
CCCAGCGAGACAGCCCCGGCCTCGGTTTTTCCCCAGAATGGAGCCGCCCGTAGGGCAGTG
GCAGCCCAGCCAGGACGGAAGCGAAAATCGAATTGTTTGGGCACTGATGAGGACTCCCAG
GACAGCTCTGATGGAATACCGTCAGCACCACGCATGACTGGCAGCCTGGTGTCTGATCGA
AGCCACGACGACATCGTCACCCGGATGAAGAACATTGAGTGCATTGAGCTGGGCCGGCAC
CGCCTCAAGCCGTGGTACTTCTCCCCGTACCCACAGGAACTCACCACATTGCCTGTCCTC
TACCTGTGCGAGTTCTGCCTCAAGTACGGCCGTAGTCTCAAGTGTCTTCAGCGTCATTTG
ACCAAGTGTGACCTACGACATCCTCCAGGCAATGAGATTTACCGCAAGGGCACCATCTCC
TTCTTTGAGATTGATGGACGTAAGAACAAGAGTTATTCCCAGAACCTGTGTCTTTTGGCC
AAGTGTTTCCTTGACCATAAGACACTGTACTATGACACAGACCCTTTCCTCTTCTACGTC
ATGACAGAGTATGACTGTAAGGGCTTCCACATCGTGGGCTACTTCTCCAAGGAGAAAGAA
TCAACGGAAGACTACAATGTGGCCTGCATCCTAACCCTGCCTCCCTACCAGCGCCGGGGC
TACGGCAAGCTGCTGATCGAGTTCAGCTATGAACTCTCCAAAGTGGAAGGGAAAACAGGG
ACCCCTGAGAAGCCCCTCTCAGACCTTGGCCTCCTATCCTATCGAAGCTACTGGTCCCAG
ACCATCCTGGAGATCCTGATGGGGCTGAAGTCGGAGAGCGGGGAGAGGCCACAGATCACC
ATCAATGAGATTAGTGAAATCACCAGCATCAAGAAGGAGGATGTCATCTCCACTCTGCAG
TACCTCAATCTCATCAACTACTACAAGGGCCAGTACATCCTCACACTGTCAGAGGACATC
GTGGATGGCCATGAGCGGGCCATGCTCAAGCGGCTCCTGCGGATCGACTCCAAGTGTCTG
CACTTCACTCCCAAGGACTGGAGCAAGAGGGGGAAGTGGTGA
Protein Properties
Number of Residues 513
Molecular Weight 56291.915
Theoretical pI 8.536
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Histone acetyltransferase KAT5
MAEVGEIIEGCRLPVLRRNQDNEDEWPLAEILSVKDISGRKLFYVHYIDFNKRLDEWVTH
ERLDLKKIQFPKKEAKTPTKNGLPGSRPGSPEREVPASAQASGKTLPIPVQITLRFNLPK
EREAIPGGEPDQPLSSSSCLQPNHRSTKRKVEVVSPATPVPSETAPASVFPQNGAARRAV
AAQPGRKRKSNCLGTDEDSQDSSDGIPSAPRMTGSLVSDRSHDDIVTRMKNIECIELGRH
RLKPWYFSPYPQELTTLPVLYLCEFCLKYGRSLKCLQRHLTKCDLRHPPGNEIYRKGTIS
FFEIDGRKNKSYSQNLCLLAKCFLDHKTLYYDTDPFLFYVMTEYDCKGFHIVGYFSKEKE
STEDYNVACILTLPPYQRRGYGKLLIEFSYELSKVEGKTGTPEKPLSDLGLLSYRSYWSQ
TILEILMGLKSESGERPQITINEISEITSIKKEDVISTLQYLNLINYYKGQYILTLSEDI
VDGHERAMLKRLLRIDSKCLHFTPKDWSKRGKW
GenBank ID Protein 27802679
UniProtKB/Swiss-Prot ID Q92993
UniProtKB/Swiss-Prot Entry Name KAT5_HUMAN
PDB IDs
GenBank Gene ID AY214165
GeneCard ID KAT5
GenAtlas ID KAT5
HGNC ID HGNC:5275
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Kamine J, Elangovan B, Subramanian T, Coleman D, Chinnadurai G: Identification of a cellular protein that specifically interacts with the essential cysteine region of the HIV-1 Tat transactivator. Virology. 1996 Feb 15;216(2):357-66. [PubMed:8607265 ]
  5. Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV: PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production. Mol Cell Biol. 2001 Jul;21(14):4470-81. [PubMed:11416127 ]
  6. Legube G, Trouche D: Identification of a larger form of the histone acetyl transferase Tip60. Gene. 2003 May 22;310:161-8. [PubMed:12801643 ]
  7. Cai Y, Jin J, Tomomori-Sato C, Sato S, Sorokina I, Parmely TJ, Conaway RC, Conaway JW: Identification of new subunits of the multiprotein mammalian TRRAP/TIP60-containing histone acetyltransferase complex. J Biol Chem. 2003 Oct 31;278(44):42733-6. Epub 2003 Sep 8. [PubMed:12963728 ]
  8. Kimura A, Horikoshi M: Tip60 acetylates six lysines of a specific class in core histones in vitro. Genes Cells. 1998 Dec;3(12):789-800. [PubMed:10096020 ]
  9. Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y: Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell. 2000 Aug 18;102(4):463-73. [PubMed:10966108 ]
  10. Lee HJ, Chun M, Kandror KV: Tip60 and HDAC7 interact with the endothelin receptor a and may be involved in downstream signaling. J Biol Chem. 2001 May 18;276(20):16597-600. Epub 2001 Mar 21. [PubMed:11262386 ]
  11. Legube G, Linares LK, Lemercier C, Scheffner M, Khochbin S, Trouche D: Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation. EMBO J. 2002 Apr 2;21(7):1704-12. [PubMed:11927554 ]
  12. Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM, Amati B: MYC recruits the TIP60 histone acetyltransferase complex to chromatin. EMBO Rep. 2003 Jun;4(6):575-80. [PubMed:12776177 ]
  13. Lemercier C, Legube G, Caron C, Louwagie M, Garin J, Trouche D, Khochbin S: Tip60 acetyltransferase activity is controlled by phosphorylation. J Biol Chem. 2003 Feb 14;278(7):4713-8. Epub 2002 Dec 4. [PubMed:12468530 ]
  14. Xiao H, Chung J, Kao HY, Yang YC: Tip60 is a co-repressor for STAT3. J Biol Chem. 2003 Mar 28;278(13):11197-204. Epub 2003 Jan 27. [PubMed:12551922 ]
  15. Doyon Y, Cote J: The highly conserved and multifunctional NuA4 HAT complex. Curr Opin Genet Dev. 2004 Apr;14(2):147-54. [PubMed:15196461 ]
  16. Legube G, Linares LK, Tyteca S, Caron C, Scheffner M, Chevillard-Briet M, Trouche D: Role of the histone acetyl transferase Tip60 in the p53 pathway. J Biol Chem. 2004 Oct 22;279(43):44825-33. Epub 2004 Aug 13. [PubMed:15310756 ]
  17. Panchenko MV, Zhou MI, Cohen HT: von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated with histone acetyltransferase activity. J Biol Chem. 2004 Dec 31;279(53):56032-41. Epub 2004 Oct 22. [PubMed:15502158 ]
  18. Doyon Y, Selleck W, Lane WS, Tan S, Cote J: Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. [PubMed:14966270 ]
  19. Taubert S, Gorrini C, Frank SR, Parisi T, Fuchs M, Chan HM, Livingston DM, Amati B: E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1. Mol Cell Biol. 2004 May;24(10):4546-56. [PubMed:15121871 ]
  20. Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, Agami R, Ge W, Cavet G, Linsley PS, Beijersbergen RL, Bernards R: A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature. 2004 Mar 25;428(6981):431-7. [PubMed:15042092 ]
  21. Col E, Caron C, Chable-Bessia C, Legube G, Gazzeri S, Komatsu Y, Yoshida M, Benkirane M, Trouche D, Khochbin S: HIV-1 Tat targets Tip60 to impair the apoptotic cell response to genotoxic stresses. EMBO J. 2005 Jul 20;24(14):2634-45. Epub 2005 Jul 7. [PubMed:16001085 ]
  22. Sun Y, Jiang X, Chen S, Fernandes N, Price BD: A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13182-7. Epub 2005 Sep 2. [PubMed:16141325 ]
  23. Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J: ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. [PubMed:16387653 ]
  24. Miyajima N, Maruyama S, Bohgaki M, Kano S, Shigemura M, Shinohara N, Nonomura K, Hatakeyama S: TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells. Cancer Res. 2008 May 1;68(9):3486-94. doi: 10.1158/0008-5472.CAN-07-6059. [PubMed:18451177 ]
  25. Cheng Z, Ke Y, Ding X, Wang F, Wang H, Wang W, Ahmed K, Liu Z, Xu Y, Aikhionbare F, Yan H, Liu J, Xue Y, Yu J, Powell M, Liang S, Wu Q, Reddy SE, Hu R, Huang H, Jin C, Yao X: Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response. Oncogene. 2008 Feb 7;27(7):931-41. Epub 2007 Aug 20. [PubMed:17704809 ]